Chi20418 811.819

A Pilot Randomized Controlled Trial of Combined
Trauma-Focused CBT and Sertraline for Childhood
JUDITH A. COHEN, M.D., ANTHONY P. MANNARINO, PH.D., JAMES M. PEREL, PH.D.,
Objective: To examine the potential benefits of adding a selective serotonin reuptake inhibitor, sertraline, versus placebo,
to trauma-focused cognitive-behavioral therapy (TF-CBT) for improving posttraumatic stress disorder and related
psychological symptoms in children who have experienced sexual abuse. Method: Twenty-four 10- to 17-year-old female
children and adolescents and their primary caretakers were randomly assigned to receive TF-CBT + sertraline or TF-CBT +
placebo for 12 weeks. Results: Both groups experienced significant improvement in posttraumatic stress disorder and
other clinical outcomes from pre- to posttreatment with no significant group Â time differences between groups except in
Child Global Assessment Scale ratings, which favored the TF-CBT + sertraline group. Conclusions: Only minimal
evidence suggests a benefit to adding sertraline to TF-CBT. A drawback of adding sertraline was determining whether
TF-CBT or sertraline caused clinical improvement for children with comorbid depression. Current evidence therefore
supports an initial trial of TF-CBT or other evidence-supported psychotherapy for most children with PTSD symptoms
before adding medication. J. Am. Acad. Child Adolesc. Psychiatry, 2007;46(7):811Y819. Key Words: cognitive-
behavioral therapy, posttraumatic stress disorder, randomized trial, sertraline.
Posttraumatic stress disorder (PTSD) is a potentially
the full disorder (Carrion et al., 2002). Left untreated,
serious mental health condition that may develop
PTSD can lead to difficulties that last into adulthood,
following traumatic events such as childhood sexual
such as increased suicide attempts, hospitalizations,
abuse. Children who have significant PTSD symptoms
substance abuse, depression, and dissociation (Warshaw
without meeting full diagnostic criteria have been shown
et al., 1993). For survivors of child abuse, these
to have comparable functional impairment to those with
problems are associated with increased use of healthcare resources (Walker et al., 1999). To minimizesuffering and prevent these long-term deleterious out-
comes, it is important to identify and test a range of
Drs. Cohen and Mannarino and Ms. Staron are affiliated with the Drexel
optimal treatments for childhood PTSD symptoms.
University College of Medicine, Allegheny General Hospital, Department of
Trauma-focused cognitive-behavioral therapy (TF-
Psychiatry, Pittsburgh; and Dr. Perel is with the University of Pittsburgh Schoolof Medicine, Western Psychiatric Institute and Clinic, Pittsburgh.
CBT) is recognized as an effective treatment for
This project was funded by an Independent Scientist grant from the National
childhood PTSD symptoms (Cohen et al., 2000;
Institute of Mental Health (K02MH01938) to Dr. Cohen. Sertraline tablets
Saunders et al., 2004). In six randomized, controlled
and identical pill placebo were donated to this project by Pfizer. The authorsthank the project therapists, research coordinator, independent evaluator, and
trials (RCTs) for sexually abused and multiply
consultants for their assistance, as well as Jeffrey Bridge, Ph.D., Rachel San
traumatized children (reviewed in Cohen et al.,
Pedro, M.S.W., and Ann Marie Kotlik for their many contributions to this
2004), TF-CBT was superior to comparison or control
project. Most of all, they thank the children and parents who participated in thisproject.
conditions in decreasing PTSD symptoms as well as
Correspondence to Dr. Judith A. Cohen, Four Allegheny Center, Eighth Floor,
improving depression, anxiety, and externalizing behav-
Pittsburgh, PA 15212; e-mail: [email protected]
ioral problems. In the largest study of TF-CBT to date
0890-8567/07/4607-0811Ó2007 by the American Academy of Child
(Cohen et al., 2004), 229 sexually abused children ages
8Y14 and their nonoffending parents were randomly
J. A M. A CA D. CHILD ADOLE SC . P SYC HIA TRY, 46: 7, JULY 2007
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assigned to receive 12 sessions of TF-CBT or child-
The study was thus reconfigured to assess the potential
centered therapy (CCT). Outcomes with TF-CBT were
benefits and risks of adding an SSRI, sertraline, versus
superior for almost all measures, with effect sizes
placebo to TF-CBT in a double-blind RCT design. Our
ranging from medium to large between the two groups
primary questions were whether adding sertraline to TF-
on the three PTSD clusters and total PTSD symptoms.
CBT could significantly improve children_s PTSD
Despite this success, 21% of the TF-CBT group
symptoms or global functioning. Our second question
continued to carry a diagnosis of PTSD. Although this
was whether the children who received sertraline would
compared favorably to the CCT group, these findings
experience more frequent and/or more severe side effects.
suggest that for a minority of children, supplementing
Exploratory questions were whether the addition of
TF-CBT with additional interventions may be neces-
sertraline produced a more favorable (i.e., faster) response
in PTSD symptoms during the course of treatment, and
Several RCTs have demonstrated that pharmacolo-
whether the addition of sertraline produced differential
gical interventions alone, particularly selective seroto-
beneficial responses in terms of other symptoms typically
nin reuptake inhibitors (SSRIs), can successfully lead to
assessed in sexually abused cohorts.
remission in adult PTSD diagnosis (Brady et al., 2000;Davidson et al., 1996; van der Kolk et al., 1994).
Potential mechanisms for this response include thatsertraline indirectly stimulates the 5-HT1A receptor and
thus would be expected to be anxiolytic (Schreiber et al.,
Funding for this project was received in April 2001 with subject
1998) and that sertraline has been shown to stimulate
recruitment beginning in January 2002. The project proposed to
the CNS neurosteroid/GABAa system (Griffin and
recruit a final cohort of 80 subjects with 40 in each treatment
Mellon, 1999). No RCTs have yet been published for
condition (TF-CBT + sertraline versus TF-CBT + placebo).
pharmacological treatments of childhood PTSD.
Information became available in 2003 that children may beexperiencing increased suicidal ideation while taking SSRIs
The typical design for a pharmacological RCT is to
(Mitka, 2003). Public warnings about antidepressant medication
randomly assign participants to medication or placebo
were issued by the U.S. Food and Drug Administration in 2003,
in a double-blind fashion, such that some children
and the eventual Bblack box[ warnings were included on SSRImedications in 2004 (U.S. Food and Drug Administration, 2004).
receive only placebo intervention. Concerns could be
Families we were attempting to recruit for the present study were
raised about comparing a medication condition to a
provided with updated information as it was issued on Web sites by
placebo condition when addressing a potentially serious
the U.S. Food and Drug Administration and the AmericanAcademy of Child and Adolescent Psychiatry with regard to
disorder such as PTSD, particularly when an effective
potential side effects of sertraline. Due to families_ concerns, the
psychosocial treatment such as TF-CBT is available,
total number of subjects recruited for this project was far below what
despite compelling cases having been made for the
benefits of conducting placebo-controlled trials (Leon,
Subjects were consecutively referred children ages 10Y17 years
who had experienced contact sexual abuse that was confirmed by
2000; Quitkin and Klein, 2000). These concerns
Child Protective Services (CPS), law enforcement, or a profes-
diminish if children in both conditions also receive a
sional independent forensic evaluator, who met all study criteria
psychosocial treatment with proven efficacy such as TF-
and agreed (along with a custodial parent or other caregiver) toparticipate in the study. Referral sources included CPS, police,
CBT, although this design would decrease the like-
victim advocacy centers, pediatric care providers, mental health
lihood of detecting differences between the medication
care providers, and self-referrals. No recruitment ads were placed.
and placebo conditions (because the majority of both
Inclusion criteria were having sexual abuseYrelated PTSDsymptoms (defined as at least five PTSD symptoms on the
groups would be expected to respond to TF-CBT alone,
Schedule for Affective Disorders and Schizophrenia for School-
thus in effect reducing the sample size). This project as
Age Children-Present and Lifetime version [K-SADS-PL] with at
originally designed proposed to evaluate the relative
least one symptom in each of the three PTSD clusters and
efficacy of sertraline versus TF-CBT for treating PTSD
clinically significant impairment), having a parent or caregiverwho was available to give consent and participate, and being
symptoms in sexually abused children by comparing
10Y17 years of age. Exclusionary criteria were non-English
TF-CBT versus sertraline versus placebo. Because the
speaking; schizophrenia or other active psychotic disorder; mental
above concerns were raised, the design was revised to
retardation or pervasive developmental disorder (all due to therequirement to receive TF-CBT, a cognitive-oriented psychother-
provide TF-CBT to all participants and to randomize
apy); or taking current psychotropic medications. Youths with
children to receive either sertraline or placebo.
substance use were not excluded from the study (in an attempt to
J. A M. ACA D. CHILD ADOL ESC. P SYC HIATRY, 46:7, JULY 2007
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include a representative sample of sexually abused youths with
study before the third treatment session due to residential
PTSD), but those with current substance dependence were not
Demographic information is presented in Table 1. Demographic
A CONSORT flowchart for this study is presented in Figure 1.
characteristics of the final cohort included in the study did not
Of the 24 participants who met the required PTSD criteria and were
significantly differ from the 31 children who did not meet criteria
randomly assigned to treatment, two did not complete the study,
leaving a final treatment cohort of 22 subjects. The two participants
According to consensus interview on the K-SADS-PL, 15
who did not complete treatment (one in each condition) left the
(68.2%) of the subjects met criteria for diagnosis other than PTSD,
Fig. 1 Flowchart. MR = mental retardation; SUD = substance use disorder; RCT = randomized controlled trial; PTSD = posttraumatic stress disorder; TF-CBT =trauma-focused cognitive-behavioral therapy.
J. A M. A CA D. CHILD ADOLE SC . P SYC HIA TRY, 46: 7, JULY 2007
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with seven subjects (63.5%) in the TF-CBT + sertraline condition
random number sequence to the TF-CBT + placebo or TF-CBT +
and eight (72.7%) in the TF-CBT + placebo condition meeting
sertraline condition. This was a double-blind procedure whereby no
criteria for at least one comorbid diagnosis. All but one of these
one directly involved in the study (i.e., parents, children,
children met criteria for major depressive disorder (MDD). Other
independent evaluator, therapists, or child and adolescent psychia-
diagnoses included general anxiety disorder, substance abuse not
trist) knew which condition the children were assigned to
otherwise specified, oppositional defiant disorder, panic disorder,
As determined by the K-SADS-PL, this cohort had experienced a
mean of 3.0 different types of previous traumas in addition to sexual
abuse, including the following: 10 (45.4%) serious accidents, 2 (9%)
The following instruments were administered by the independent
disasters, 6 (27.2%) violent crime, 17 (77.3%) traumatic death or
evaluator: K-SADS-PL (Kaufman et al., 1996) is a semistructured
life-threatening illness, 4 (18.2%) domestic violence, 2 (9.1%)
interview administered independently to child and parent to assess
physical abuse, and 4 (18.2%) other PTSD-level traumas.
the presence of DSM-IV psychiatric disorders. For the purposes ofthis study only, the PTSD section was readministered posttreat-
ment; the other sections were administered pretreatment to assesschildren for exclusionary criteria only. For the present sample,
Upon referral, a telephone screen was conducted and the
interrater reliability Cohen_s . for K-SADS-PL-PTSD diagnostic
possibility of participating in the study was discussed with parents.
status (yes/no) was 0.92. The CGAS (Shaffer et al., 1983) is a 0- to
Those who agreed were scheduled for an initial assessment, which
100-point scale on which an independent rater evaluates the child_s
was conducted by an independent evaluator. This evaluator was
global impairment. The CGAS is highly correlated with children_s
trained in administration of the K-SADS-PL and the Children_s
general functional competence and is not highly correlated with
Global Assessment Scale (CGAS). The evaluator continued to be
other measures of symptom severity (Green et al., 1994). For the
randomly checked throughout the course of the study to ensure
present sample, Pearson_s correlation interrater reliability of the
ongoing interrater reliability with regard to both instruments. At the
CGAS was 0.90. The CGAS was completed pretreatment and at
initial evaluation, children and parents completed the initial
assessment instruments described below and those who qualified
Children completed the following instruments pre- and
for admission to the study read and signed informed assent/consent
posttreatment. The Children_s PTSD Symptoms Scale (CPSS;
forms. Children were randomized according to a computerized
Foa et al., 2001) is a 24-item self-report measure of PTSD. Test-retest reliability for the CPSS is 0.84. The Mood and FeelingsQuestionnaire (MFQ; Costello and Angold, 1988) is a 33-item
self-report measure of child and adolescent depression. Test-retest
reliability for the MFQ is 0.85. Clinical cutoff score for thisversion of the MFQ is 28. (Note: Children additionally completed
the CPSS and MFQ at weeks 3, 5, and 8.) The Screen for
Children_s Anxiety Related Emotional Disorders (SCARED;
Birmaher et al., 1997) is a 38-item self-report measure for
children_s anxiety symptoms with good (0.86) test-retest reliability.
Clinical cutoff score for the SCARED is 25. The Children_sAttributions and Perceptions Scale (Mannarino et al., 1994) is a
self-report instrument in which children report their child
abuseYrelated attributions and perceptions related to self-blame,
feeling different from peers, feelings of not being believed, and loss
of interpersonal trust. Test-retest reliability for the Children_s
Attributions and Perceptions Scale is 0.75.
Parents completed the following instruments pre- and posttreat-
ment. Child Behavior Checklist (Achenbach, 1991) is a 118-item
parent report form for children_s behaviors. Reliability is 90.90 for
the broadband scales used in this study. Beck Depression Inventory
II (Beck et al. 1996) is a parent self-report of depression. Test-retestreliability for the BDI-II is high (0.93). Cutoff score for a nonclinical
population on the BDI is 12. The Parent_s Emotional Reaction
Questionnaire (Mannarino and Cohen, 1996) is a self-report
measure of parental emotional distress related to the child_s sexual
abuse; test-retest reliability is 0.90; the Parental Support Ques-
tionnaire (Mannarino and Cohen, 1996) is a self-report ques-
tionnaire of parental support of the child and attributions about
responsibility for the abuse. Test-retest reliability for the Parental
The child and adolescent psychiatrist assisted parents and children
in completing the following form at each medication evaluationsession. The Side Effects Form for Children and Adolescents
Mean no. of months since most recent abuse
(SEF-CA; Klein, 1998) is a child- and caretaker-informed form to
J. A M. ACA D. CHILD ADOL ESC. P SYC HIATRY, 46:7, JULY 2007
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be completed regarding psychotropic medication side effects. Each
item is completed regarding frequency and severity.
Data analyses were conducted using SPSS version 14. A series of
repeated-measures analyses of covariance (ANCOVAs) were
conducted with the covariate in each analysis being the pretreatmentscore for the outcome score posttreatment under analysis. The
Identical pill sertraline (25 and 50 mg) and pill placebo were
ANCOVAs of the K-SADS-PL-PTSD were conducted separately
provided free of charge to this study by Pfizer. Pfizer had no
because those were the only data collected through a semistructured
other involvement in the study. At the initial evaluation session, a
interview. The CGAS is not highly correlated with measures of
psychiatric evaluation was performed. The same child and
symptomatology (Green et al., 1994), and for this reason, a separate
adolescent psychiatrist performed this evaluation for all of the
children in the study and conducted subsequent medication
Due to the large number of other overlapping child and parent
management appointments. The initial psychiatric evaluation
self-report measures included in the study, a multivariate analysis of
included obtaining relevant psychiatric history, obtaining permis-
covariance was conducted to determine whether overall differences
sion to receive the child_s primary care provider records including
between the two treatment groups were present from pre- to
the most recent physical examination; inquiring about possible
posttreatment, before performing ANCOVAs on individual instru-
pregnancy if appropriate; reviewing current medications; review-
ments. These multivariate analysis of covariances and ANCOVAs
ing current and past medical conditions; and reviewing sertraline
only included pre- and posttreatment data. To examine potential
information (mechanisms of action, risks, benefits, side effects,
differences between the two groups with regard to side effects, data
dose, and administration). The child and parent were given
from the SEF-CA were compared using a two-tailed Fisher exact
written information about sertraline, and a urine sample was
test. To examine suicidality, responses to BI thought about killing
obtained for urine drug screen, urinalysis, and urine pregnancy
myself [ on the MFQ were examined separately at sessions 1, 3, 5, 8,
test (if postmenarchal). The child and parent then were
and 12. Chi-square analyses were performed to compare differences
interviewed individually by the child and adolescent psychiatrist
in responses between the two groups.
The child and parent were seen for medication checks at sessions
1, 3, 5, 8, and 12, with sertraline/placebo dose titrated as follows.
Pills were started at 25 mg/day for 3 days for all subjects, withinstructions to increase the dose to 50 mg/day to be continued at a
There were no significant differences between the
dose of 50 mg/day for the first 2 weeks. At the second appointment(week 3), subjects completed the CPSS and MFQ at the medication
two groups on any demographic variables at pretreat-
management session. Subjects whose CPSS indicted clinically
ment. As shown in Table 2, on the K-SADS-PL-PTSD,
significant improvement of symptoms from their initial score,
although there was a highly significant effect for time,
and/or whose side effects were judged sufficiently severe to warrant
there were no significant group Â time differences with
holding the dose at 50 mg/day were instructed to maintain this dose.Subjects whose symptoms were not judged to be significantly
regard to improvement in PTSD symptoms from pre-
improved and/or whose side effects were not judged to be severe were
to posttreatment. However, effect sizes were medium in
instructed to increase the dose to 100 mg/day for the next 2 weeks.
Dose titration continued in this manner at each medicationcheck, to a maximum of 200 mg/day. Mean maximum dose reached
There was a significant group Â time interaction
for the TF-CBT + sertraline group was 150 mg/day (range 50Y200
with regard to the CGAS (Table 3). The largest
mg/day). Mean maximum dose reached for the TF-CBT + placebo
single incremental improvement in CGAS scores in
group was 172.73 mg/day (range 50Y200 mg/day). Dose for theTF-CBT + placebo group was higher at each point in treatment
the TF-CBT + sertraline group occurred between weeks
from week 5 onward. This difference in dose between the two
3 and 5, a time during which the pharmacological action
groups approached significance ( p = .078).
of sertraline could be expected to become noticeable.
The multivariate analysis of covariance showed a
significant effect for time (F = 13.59, p < .001) but not
TF-CBT is described in detail elsewhere (Cohen et al., 2006;
for group (F = 0.986, p = .51) or group Â time (F = 1.23,
Deblinger and Heflin, 1996; TF-CBT Web, 2005). The primary
p = .37). However, because of the significant time effect,
components are summarized by the acronym PRACTICE: parenting
we examined which instruments changed significantly
skills, psychoeducation, relaxation, affect modulation, cognitiveprocessing, trauma narrative, in vivo mastery of trauma reminders,
over time by conducting univariate ANOVAs for the
conjoint child-parent session, and enhancing safety, healthy sexu-
entire cohort. The MFQ, SCARED, CPSS, CBCL
ality, and future development. In the present study TF-CBT was
Total, Parent_s Emotional Reaction Questionnaire,
provided over the course of 12 weeks, in 12 parallel sessions forchildren and their parents/caretakers. TF-CBT was provided by one
BDI, and Parental Support Questionnaire showed
of two randomly assigned clinicians. Both therapists were licensed
significant (<.05) change from pre- to posttreatment.
master_s degreeYlevel social workers. Treatment sessions were
The two groups showed no significant differences
audiotaped for adherence to the TF-CBT model, and all sessionswere required to meet 990% adherence to the model through the use
with regard to side effects at any point in the study as
measured by the SEF-CA. They also showed no
J. A M. A CA D. CHILD ADOLE SC . P SYC HIA TRY, 46: 7, JULY 2007
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Repeated-Measures ANCOVA for PTSD Symptoms
Note: ANCOVA = analysis of covariance; PTSD = posttraumatic stress disorder.* p < .001.
significant difference with regard to responses to the
improvement on any instrument. The numbers of
question about suicidal ideation on the MFQ at any
participants attaining clinically meaningful improve-
point during the study, with equivalent proportions of
children experiencing decreased suicidal ideation in
PTSD Diagnosis. Two of the participants were in the
both groups during the course of the study. No
no-PTSD diagnosis category at pretreatment (both in
participant in either group developed new onset of
the TF-CBT + sertraline group). At posttreatment, 14
suicidal ideation during the course of the study.
additional participants had moved into the no-PTSDdiagnosis or nonclinical range in this regard (eight
TF-CBT + sertraline; six TF-CBT + placebo).
Adverse events were defined as suicide attempts,
Global Impairment Status. At pretreatment, all 22
reportable child abuse episodes, drug overdoses, or
participants were in the clearly impaired (CGAS <60)
psychiatric hospitalizations. One participant in the
range on the CGAS. At posttreatment, 15 had moved
TF-CBT + sertraline group was hospitalized overnight
into the not clearly impaired range on the CGAS (nine
during week 12 for oppositional defiant disorder
TF-CBT + sertraline, six TF-CBT + placebo).
symptoms after running away from home. This child
Other Clinical Instruments. On the SCARED, four
had a history of oppositional defiant disorder and
participants (two in each group) scored in the
running away, which preceded this treatment study.
nonclinical range (score <25) at pretreatment; at
No other adverse events were reported during the
posttreatment 13 additional participants had improved
into the nonclinical range (eight TF-CBT + sertraline;five TF-CBT + placebo).
On the MFQ, nine participants scored in the
There was no significant difference between the two
nonclinical range (score <27) at pretreatment (three
treatment groups with regard to clinically meaningful
TF-CBT + sertraline; six TF-CBT + placebo); at
CGAS-Sertraline 45.09 (5.24) 50.09 (5.36) 59.45 (6.82) 61.18 (8.62) 66.64 (10.12)
46.64 (5.03) 51.64 (4.23) 50.64 (9.12) 54.73 (8.84) 59.55 (9.70)
Note: ANCOVA = analysis of covariance; CGAS = Children_s Global Assessment Scale.* p < .01; ** p < .001.
J. A M. ACA D. CHILD ADOL ESC. P SYC HIATRY, 46:7, JULY 2007
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posttreatment, 13 additional participants had moved
(ANCOVA), calculated that at least 32 treatment
into the nonclinical range (eight TF-CBT + sertraline;
completers per group would be needed to achieve
five TF-CBT + placebo). With regard to suicidal ideation
adequate power when comparing the TF-CBT + placebo
at pretreatment, five participants responded Btrue[ to the
versus and TF-CBT + sertraline groups. Clearly the final
question BI thought about killing myself[ (four TF-CBT
sample size of this study is too small to allow us to draw
+ sertraline, one TF-CBT + placebo). At posttreatment,
any definitive conclusions about possible benefits or lack
no participants responded Btrue[ to this question.
thereof of adding sertraline to TF-CBT for this
On the CBLC Total score, at pretreatment four
participants had scores in the nonclinical range (T score
The current findings are promising in that only
<60; three TF-CBT + sertraline, one TF-CBT + placebo).
one adverse event (likely unrelated to medication)
At posttreatment eight additional participants had
occurred among children receiving sertraline, despite
moved into the nonclinical range (four in each group).
the fact that they received substantial doses of this
On the BDI eight parents had scores in the normal
medication (mean maximum dose of 150 mg/day).
range at pretreatment (four in each group); at posttreat-
Among the 11 children and adolescents participating
ment, six more had moved into the normal range (four
in this study who received sertraline, none developed
TF-CBT + sertraline, two TF-CBT + placebo).
significant suicidal symptoms. Although this is a smallnumber of children on which to base any conclusionsof safety, the fact that the side effects reported were
also relatively low is encouraging. It is possible that
This study attempted to conduct an RCT to evaluate
the early components of TF-CBT, which provide
the benefit of adding sertraline to TF-CBT for sexually
individualized relaxation and affective modulation
abused children with PTSD symptoms. This cohort
interventions, helped to reduce the prominence of
was not representative of sexually abused children
requesting clinical treatment due to the refusal of many
This study points out the substantial difficulty of
families to consider pharmacological treatments for
recruiting a clinically representative sample with which
their children, and conclusions drawn from this study
to conduct a child psychopharmacological RCT among
must be evaluated in this context. There were no
traumatized children. One third of the potential cohort
significant group Â time differences between the two
pool (59/176) refused to consent to participate in this
groups with regard to remission of PTSD symptoms or
study, largely based on the possibility of receiving active
other clinical symptomatology. The only statistically
medication. Although it is impossible to prove that this
significant difference in outcome between the groups
difficulty was related to parental concerns regarding the
was on the CGAS, and this clinically observed
potential association between SSRIs and suicidality in
improvement corresponded with the time at which
children, it is interesting to note that 20 of 24 of the
clinical improvement may be expected to occur based
subjects who were randomized in this treatment trial
on the pharmacological properties of sertraline. The
were recruited within the first 18 months of recruit-
fact that both groups improved significantly and
ment (January 2002YJuly 2003), with only four
equivalently with regard to not only PTSD but also
additional subjects being successfully recruited from
depression, anxiety, behavior problems, and a variety of
July 2003 to January 2006. If there was a systematic
parental scores supports the idea that the treatment
sampling bias in the present cohort, then one could
effect observed was due to TF-CBT interventions rather
reasonably speculate that it was more positively
than sertraline. However, this finding must be taken in
predisposed toward psychotropic medication use in
the context of the fact that the study was inadequately
powered to detect significant differences between thetwo treatment groups.
An initial power analysis using the Sample Power 1.0
Limitations of this study include the small sample
program of Borenstein et al. (1997), which allowed for
size, the self-selected nature of the cohort, and the lack
the need to enter covariates, a medium effect size, and
of a representative sample with regard to gender or
the need to conduct one-way fixed effects of covariance
ethnic diversity other than African American youths.
J. A M. A CA D. CHILD ADOLE SC . P SYC HIA TRY, 46: 7, JULY 2007
Copyright @ 2007 American Academy of Child and Adolescent Psychiatry. Unauthorized reproduction of this article is prohibited.
combination with psychotherapy. It is also important to
Although children in both groups experienced
note that in many cases, combined TF-CBT + sertraline
equivalent improvement in all domains except CGAS
can be provided as a short-term or time-limited treat-
scores, at the end of the study, decisions had to be made
ment modality. Most participants (7/11) who received
as to whether TF-CBT + sertraline participants should
this modality were able to tolerate tapering off a
continue taking sertraline or taper off this medication.
relatively high dose of sertraline within 1Y3 months,
Because seven of these participants met criteria for
including three participants who had comorbid MDD.
MDD at the start of the study, and all of these
In conclusion, this study found that for a small and
participants responded positively to treatment with
self-selected group of multiply traumatized sexually
regard to improvement in depression scores, it was not
abused girls, TF-CBT + sertraline was not superior to
possible to determine whether this response was due to
TF-CBT + placebo except with regard to CGAS
TF-CBT, sertraline, or a combination of both treat-
outcomes. However, because the study was statistically
ments. The practice parameters in place at the time
underpowered, no definitive conclusions can be drawn
suggested that continuation treatment be maintained
about the potential benefit or lack thereof of adding
for at least 6 months following remission (American
sertraline to TF-CBT for this population. A potential
Academy of Child and Adolescent Psychiatry, 1998),
drawback of starting combined treatment was that once
and thus in cases in which MDD symptoms have been
a child responded positively, it was not possible to know
prominent, it was difficult to justify discontinuing the
whether the response was to psychotherapy, medication,
medication once it was started. This was particularly
or both, and this may have led to unnecessary
true when depressive symptoms intermittently in-
prolongation of pharmacological treatment. Due to
creased after the end of the study (e.g., when legal
the failure of this pilot trial to demonstrate a clear
proceedings occurred related to sexual abuse charges).
benefit of adding sertraline, treatment in most cases
In other cases, the child and adolescent psychiatrist
should begin with TF psychotherapy with proven
suggested tapering medication, but the child and/or
efficacy such as TF-CBT. Medication should be added
parent were reluctant to do so due to concerns about
only when and if an individual child_s situation
symptoms returning if medication was discontinued.
Although TF-CBT treatment ended after the 12thtreatment session, 4 of the 11 TF-CBT + sertraline
Disclosure: The authors have no financial relationships to disclose.
participants continued sertraline for more than 4months. The remaining seven tapered and discontinuedsertraline within 1Y4 months after the end of the study.
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Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, andthe Hippocampus Victor G. Carrion, MD, Carl F. Weems, PhD, Allan L. Reiss, MD
Objective: Does stress damage the brain? Studies of adults with posttraumatic stress disorder have demonstrated smallerhippocampal volumes when compared with the volumes of adults with no posttraumatic stress disorder. Studies of children withposttraumatic stress disorder have not replicated the smaller hippocampal findings in adults, which suggests that smallerhippocampal volume may be caused by neurodevelopmental experiences with stress. Animal research has demonstrated that theglucocorticoids secreted during stress can be neurotoxic to the hippocampus, but this has not been empirically demonstrated inhuman samples. We hypothesized that cortisol volumes would predict hippocampal volume reduction in patients withposttraumatic symptoms. Patients and Methods: We report data from a pilot longitudinal study of children (n = 15) with history ofmaltreatment who underwent clinical evaluation for posttraumatic stress disorder, cortisol, and neuroimaging. Results:Posttraumatic stress disorder symptoms and cortisol at baseline predicted hippocampal reduction over an ensuing 12- to 18-month interval. Conclusions: Results from this pilot study suggest that stress is associated with hippocampal reduction in childrenwith posttraumatic stress disorder symptoms and provide preliminary human evidence that stress may indeed damage thehippocampus. Additional studies seem to be warranted. Pediatrics 2007;119:e509Ye516.
J. A M. A CA D. CHILD ADOLE SC . P SYC HIA TRY, 46: 7, JULY 2007
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